Cutaneous T-cell lymphoma (CTCL) is a malignancy of skin-trafficking CD4+ T-cells. There presently is no marker that has been identified as being uniquely expressed on the malignant T-cells in CTCL. Therefore, the early diagnosis, as well as the ability to carefully follow the clinical course in response to treatment, can be compromised by the inability to precisely distinguish the malignant cells from normal infiltrating and/or circulating CD4+ T-cells. Our preliminary studies utilizing assays of gene expression, QPCR and flow cytometry have permitted our group to identify a marker, CD164, that, although expressed on some non- lymphocytic tissues, may be uniquely expressed on the malignant T-cells of CTCL patients while not being expressed on the non-malignant T-cells of CTCL patients, nor on the T-cells of healthy volunteers or patients with other skin inflammatory disorders including atopic dermatitis. In this proposal, using a robust number of patient samples, we plan to confirm that CD164 is expressed on the malignant CD4+ T-cells and not on normal T-cells, both in the skin and the blood, and that expression is highly correlated with, and is in fact superior to, the current state of the art methods for distinguishing the malignant T-cells. The use of such a marker would permit both the early diagnosis of disease and would enhance the ability to monitor response to therapy. Importantly, it could also serve as a future therapeutic target. This work will be applied to one of the largest populations of CTCL patients in the U.S. that are evaluated in the Penn Cutaneous Lymphoma Program.